NEONICOTINOID INSECTICIDES (e.g. thiamethoxam, imidacloprid, clothianidin) developed at Bayer Japan as safer alternatives (e.g. to human spray applicators) to the natural nicotine once widely used by farmers and gardeners, is now suspected of contributing to honey bee health problems like learning disorders and colony collapse. In contrast, natural nicotine, found in honey produced by bees working tobacco fields, as well as in pollen, nectar, leaves and other plant parts, is a nutrient and medicine helping to heal weak honey bee colonies, said Susan Nicolson of South Africa’s University of Pretoria at “Entomology Without Borders,” a joint meeting of the International Congress of Entomology (ICE) and the Entomological Society of America (ESA) in Orlando, FL.

Natural nicotine, even if produced organically in a sustainable recycling sort of way from tobacco waste products, is mostly shunned in organic farming and gardening. “Over 120 million sites will be returned on a web search on tobacco, but most will not be associated with plant science,” wrote USDA-ARS researcher T.C. Tso in Tobacco Research and Its Relevance to Science, Medicine and Industry. “Many plant scientists in academic institutions cannot obtain grant support for projects using tobacco as a research tool. Some even have to avoid tobacco because of the applying of ‘political correctness’ to academic research. The tobacco plant has served as a valuable tool since the dawn of plant and biological sciences, so it is indeed a great loss to scientific progress that a research tool already invested with so many resources and about which there is such abundant knowledge and such great potential for new advancement is now being wasted.”

Honey bees readily consume bitter alkaloids such as nicotine mixed in sugary plant nectars. Adult honey bees excel at detoxifying alkaloids such as nicotine, which should not be surprising, as survival depends on it. Younger, larval honey bees have fewer enzymes to detoxify nicotine, but also survive quite well even when their royal jelly contains high levels of nicotine. Honey bees and insects immune to nicotine, such as green peach (peach-potato) aphids, transform nicotine into less toxic butanoic acid. A knotty question naturally arises: If natural nicotine heals honey bees, why are synthetic neonicotinoids so terribly different? Are natural compounds like nicotine inherently more beneficial and their synthetic analogs (e.g. neonicotinoids) inherently bad, perhaps due to subtle differences in molecular structure? If bees and other pollinators are a major concern, perhaps natural product restrictions on nicotine need to be relaxed to provide competition to the synthetic neonicotinoids.

“Alkaloids, especially in the nicotine family, have been the main focus of tobacco research because alkaloids are the characteristic product of tobacco,” writes Tso. Dozens of other tobacco molecules are relatively overlooked, including sugar compounds providing least-toxic botanical insect and mite control. Anabasine (neonicotine), an alkaloid found in tobacco and other plants, has also been widely used as a natural insecticide. Strangely enough, anabasine is also an insect attractant and a poison gland product of Aphaenogaster ants. In a strange urban twist to the wild bird practice of lining nests with medicinal herbs emitting essential oils counteracting parasites: Researchers in Mexico discovered urban birds lining nests with cigarette butts to similar advantage. In times past, organic gardeners soaked cigarette butts in water to get a nicotine spray brew. Historically, most commercial nicotine insecticide used on farms and gardens was a sustainable tobacco waste extract.

There are 60-80 described tobacco or Nicotiana species, some available in seed catalogs and grown as ornamentals. Most Nicotiana species grow wild in the Americas, with some in Australia and Africa. “Tobacco plants are easy to grow and have a short growing period,” writes Tso. “Each tobacco plant may produce 14 g or about 150,000 seeds which may provide seedlings for 2 to 5 acres (1–3 ha) of field tobacco, depending on the type.” In Europe, oil extracted from tobacco seeds is being explored for an alternative bio-diesel fuel industry, with dry leftovers as animal feed.

Native American Nicotiana species are being integrated into China’s ancient agricultural interplanting tradition. When tobacco is interplanted in vineyard rows, tobacco roots and grape roots intermingle. Perhaps some sort of biological soil fumigation occurs. Whatever the mechanism, vineyards are cleansed of soil-dwelling phylloxera aphids, a pest that almost destroyed wine grape growing in France in the 1800s and is still a worldwide problem. According to the journal Chinese Tobacco Science, intercropping tobacco with sweet potato also alleviates soil and other pest problems, maximizing profits per unit area of land. Burley tobacco is intercropped with cabbage and other vegetable crops, according to the Journal of Yangtze University (Natural Science Edition).

Neonicotinoids are soluble in water and absorbed systemically by plants, and some are sprayed on urban lawns and landscapes. However, over 80% of synthetic neonicotinoids are applied to seeds prior to planting hundreds of millions of acres of corn, soybean, sunflowers and other crops. In Canada’s Ontario and Quebec provinces, 100% of corn seed is treated with neonicotinoids, said Nadejda Tsvetkov of Toronto’s York University at “Entomology Without Borders.” Though neonicotinoids were seldom found in corn pollen samples, somehow, perhaps by water transport, neonicotinoids are finding their way into clover and willow tree pollen far from corn fields.

“For a lot of farmers it is hard to get seeds untreated, especially corn,” as commercial seed is routinely treated with neonicotinoids regardless of need, said the University of Maryland’s Aditi Dubey at “Entomology Without Borders. In Maryland and other mid-Atlantic USA states where low pest pressures are the norm, neonicotinoid seed treatments are both unneeded and counterproductive. In 3-year Maryland rotations with double-cropped soybeans, winter wheat and corn, sowing seeds treated with thiamethoxam or imidacloprid reduced beneficial predatory ground beetles and increased slug damage to crops. Mid-Atlantic USA farmers typically apply 4 unnecessary prophylactic seed treatments every 3 years. Besides reduced biocontrol and more pest damage, soil accumulation over time is a disturbing agro-ecosystem possibility.

Alternative seed treatments include natural plant hormones such as salicylic acid and methyl jasmonate, which induce a natural immunity called induced systemic acquired resistance (SAR). Crops such as lettuce and argula (rocket) grown from seed treated with salicylic acid and methyl jasmonate also release volatile gases repelling pests such as sweet potato whitefly, a major worldwide pest, said Ben-Gurion University’s Mengqi Zhang at “Entomology Without Borders,” a gathering of 6,682 delegates from 102 countries. Numerous botanical materials and microbes have also been investigated around the world as alternative seed treatments.

A proactive approach to honey bee and bumble bee health includes a diversified landscape sown with herbs and medicinal botanicals for self-medication, not just natural nicotine from tobacco nectar or other sources. Thymol, an essential oil found in thyme and many other plants, is already sprayed in hives by beekeepers to combat Varroa mites. At “Entomology Without Borders,” North Carolina State University’s Rebecca Irwin reported laboratory choice tests where bumble bees rejected nicotine. In field tests, bumble bees were given a choice of different colored flowers each with a different botanical such as thymol, nicotine, anabasine and caffeine. Bumble bees only selected flowers with thymol to self-medicate. Interestingly, thymol and other herbal essential oils also synergize nicotine, boosting effectiveness against disease pathogens and perhaps also minimizing the likelihood of colony collapse.

Bee pharmacology is also useful in human medicine. In Oaxaca, Mexico gangrene is stopped and wounds are healed by combining maggot therapy and honey, reported Alicia Munoz. Maggot therapy uses sterilized (germ-free) green bottle fly maggots to disinfect and cleanse wounds by eating unhealthy tissues and secreting antibiotics, allowing healthy pink tissue to grow back under honey-soaked gauze. This cost-effective approach reduces hospital stays, lowers morbidity and can eliminate the need for surgery. It may sound yucky, but for diabetics and patients with bed sores or wounds where surgery is medically impossible, a few maggots and a little honey is preferable to amputating wounded or infected limbs.

Cancer-fighting bee propolis products were touched upon at “Entomology Without Borders” by Chanpen Chanchao of Chulalongkorn University in Bangkok, Thailand, where hives of stingless bees are reared like conventional honey bees. Cardol, a major component of propolis from the Indonesian stingless bee, Trigona incisa, causes early cancer cell death by disrupting mitochondrial membranes and “producing intracellular reactive oxygen species (ROS).” ROS are essential to energy, immunity, detoxification, chemical signaling, fighting chronic and degenerative diseases, etc. Cardol “had a strong antiproliferative activity against SW620 colorectal adenocarcinoma,” killing colon cancer cells within 2 hours, followed by complete cell necrosis within 24 hours. Thus, cardol is an “alternative antiproliferative agent against colon cancer.”

SYNTHETIC OR NATURAL? Which is best? Since the 1950s the synthetic chemical DEET (N, N-diethyl-m-toluamide) has been the standard to which all other mosquito, tick and biting fly repellents have been compared. DEET is still the standard of comparison, but the long search for natural or organic repellents is finally yielding a number of potential alternatives, some from the plant world and others from such unlikely places as human sweat.

The progress in besting DEET has been so stunning that the Entomological Society of America (ESA) presented a four-hour symposium with a dozen 20-minute talks, Celebrating the Success of Global Insect Repellent Science Research. Habitues of the ESA know that in the world view of a female mosquito, humans are little more than scented apes put on Earth to be protein-rich blood meals to begat new generations of what we call vermin and they consider kin.

Sweat, heat, and carbon dioxide, that greenhouse gas that humans respire into the atmosphere with every exhaled breath, tip off mosquitoes and other bloodsuckers that the human food wagon has arrived. Actually, that’s putting it a bit crudely. Mosquitoes are actually connoisseurs, and sniff out humans like a gourmet would a fine wine. To be even more accurate, females are the true connoisseurs and gourmands, the bloodsucking vampire sex of the mosquito world. Male mosquitoes are true flower children, pacifists abhorring the bloodsucking life and mostly passing the time pollinating plants.

Longtime scholars of mosquito feeding habits on humans, like Willem Takken at Wageningen University in The Netherlands, have tallied 300 to 350 compounds mosquitoes can use to identify humans. About 60 of these odors are common to every person, and the rest give each human a slightly different scent. Thus, we oftentimes remember a person by their distinctive smell. Elegant experimental techniques like gene silencing and transferring mosquito olfactory genes to fruit flies allows the mapping of mosquito odor preferences. Some mosquito species, such as the malaria-vector Anopheles gambiae, can zero right in on humans. Other mosquito species may bypass humans in favor of cows, livestock or other animal species.

From a practical standpoint, if diseases like malaria, dengue and yellow fever are not a concern and you need protection for only an hour or two, one of the many commercial botanical repellents is likely to suffice as an alternative to DEET. Lemon eucalyptus products, including Quwenling from China, get high marks from the CDC. Daniel Strickman at the USDA-ARS in Beltsville, MD, and others have compiled long lists of botanicals good for about an hour of repellency, including: clove, geranium (geraniol), citronella, celery, lemon, lime, neem, pyrethrum, fringed rue, patchouli, pennyroyal, soybean, thyme, niaouli (Melaleuca viridiflora), makaen (Zanthoxylum limonella), Mexican tea (Chenopodium ambrosioides), Labrador tea (Ledum groenlandicum), and lily-of-the-valley.

However, natural or organic does not automatically mean safe or lacking in toxicity. Natural compounds, like synthetics, can also be sources of skin irritation, toxicity, and carcinogenicity. Even lemon eucalyptus oil can be an eye irritant. And as some herbal tea drinkers have learned the hard way (as is documented in the medical journals), the active ingredients in pennyroyal, violets and other botanicals can be dangerously toxic in too high a dose or with prolonged use.

The U.S. EPA can give what is known in legalese as FIFRA 25(b) Exemptions (Minimum Risk Pesticides), the USDA’s Strickland told the ESA repellent symposium. This allows some natural compound active ingredients to be used as repellents without testing. Examples include cedar oil (from eastern red cedar), citronella, garlic, geranium, lemongrass, peppermint, soybean oil and thyme. The International Fragrance Association investigates active ingredients to avoid lawsuits over cosmetics, though even this is not a guarantee against allergic reactions.

In short, caution is the watchword. Try a little bit first, and to be really safe use long sleeves and pants so that minimal repellent directly contacts the skin (as both natural and synthetic chemicals may penetrate the skin and enter the bloodstream).

Joel Coats’ lab at the University of Iowa provided the ESA symposium with a glimpse of the future. Coats’ lab is well-known in entomological circles for its pioneering work with naturally occurring monoterpene and sesquiterpene chemicals in plants such as catnip (Nepeta cataria), Osage orange (Maclura pomifera), West Indian sandalwood (Amyris balsamifera), and Siam-wood (Fokenia hodginsii). In short, the chemicals known as monoterpenes provide a broad spatial repellency, and the “oxygenated sesquiterpenes” provide contact repellency. And a mixture of the two provides both modes of action and the best repellency. You will probably want to wait for the testing to be completed and commercial products to be formulated.

But back to the question of which is best, natural or synthetic. Some of the best natural compounds, and there are too many to list, can outperform DEET. Even some new synthetics can outperform DEET in some ways. If you have a job that keeps you in the field and exposed to mosquitoes, biting flies and ticks for 12 or 24 hours at a time, then you need some heavy-duty, long-lasting protection. Indeed, that is the holy grail for organizations like the U.S. Army.

Life may have seemed simpler in the 1960s when Mr. Robinson told Dustin Hoffman in the movie The Graduate that the future was in plastics. Quantitative structure-activity relationships (QSAR) is the future in 2010, say Coats and his graduate student Gretchen Paluch. They forsee a leapfrogging future where natural repellents better than DEET lead to new synthetic spinoffs of nature’s best molecules better than anything yet known.

They believe that patchouli, cedar oil and other natural compounds can (via QSAR) provide the skeleton for designing new repellent molecules. However, it may not be so simple, as a fine ecological balance has evolved in nature. Though it may seem contradictory, even so-called repellent plants like catnip, which is famous for repellent molecules like neptalactone, also contain attractant molecules. Possibly the best repellents will also contain elements of attraction. But that is another story for another time.